Temperature-dependent sex determination is a notable model of phenotypic plasticity. In many reptiles, including the red-eared slider turtle (), the individual's sex is determined by the ambient temperature during egg incubation. In this study, we show that the histone H3 lysine 27 (H3K27) demethylase KDM6B exhibits temperature-dependent sexually dimorphic expression in early embryos before the gonad is distinct. Knockdown of at 26°C (a temperature at which all offspring develop into males) triggers male-to-female sex reversal in >80% of surviving embryos. KDM6B directly promotes the transcription of the male sex-determining gene by eliminating the trimethylation of H3K27 near its promoter. Additionally, overexpression of is sufficient to rescue the sex reversal induced by disruption of This study establishes causality and a direct genetic link between epigenetic mechanisms and temperature-dependent sex determination in a turtle species.

These results indicate that the infiltration of inflammatory cells contributes to the pathogenesis of thoracic aortic aneurysms. Superantigen-driven stimulation of T lymphocytes in the aortic tissues of patients with thoracic aortic aneurysms may contribute to the initial immune response.

The molecular mechanism underlying temperature-dependent sex determination (TSD) has been a long-standing mystery; in particular, the thermosensitive genetic triggers for gonadal sex differentiation are largely unknown. Here, we have characterized a conserved DM domain gene, Dmrt1, in the red-eared slider turtle Trachemys scripta (T. scripta), which exhibits TSD. We found that Dmrt1 has a temperature-dependent, sexually dimorphic expression pattern, preceding gonadal sex differentiation, and is capable of responding rapidly to temperature shifts and aromatase inhibitor treatment. Most importantly, loss-and gain-of-function analyses provide solid evidence that Dmrt1 is both necessary and sufficient to initiate male development in T. scripta. Furthermore, the DNA methylation dynamics of the Dmrt1 promoter are tightly correlated with temperature and could mediate the impact of temperature on sex determination. Collectively, our findings demonstrate that Dmrt1 is a candidate master male sex-determining gene in this TSD species, consistent with the idea that DM domain genes are conserved during the evolution of sex determination mechanisms.

Phosphoglycerate mutase 1 (PGAM1) is a glycolytic enzyme that coordinates glycolysis and biosynthesis to promote cancer growth via its metabolic activity. Here, we report the discovery of a non-metabolic function of PGAM1 in promoting cancer metastasis. A proteomic study identified α-smooth muscle actin (ACTA2) as a PGAM1-associated protein. PGAM1 modulated actin filaments assembly, cell motility and cancer cell migration via directly interacting with ACTA2, which was independent of its metabolic activity. The enzymatically inactive H186R mutant retained its association with ACTA2, whereas 201-210 amino acids deleted PGAM1 mutant lost the interaction with ACTA2 regardless of intact metabolic activity. Importantly, PGAM1 knockdown decreased metastatic potential of breast cancer cells in vivo and PGAM1 and ACTA2 were jointly associated with the prognosis of breast cancer patients. Together, this study provided the first evidence revealing a non-metabolic function of PGAM1 in promoting cell migration, and gained new insights into the role of PGAM1 in cancer progression.